Clinical Trials/NCT04019561

NCT04019561

Completed

Phase 2

A Phase 2, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety and Pharmacodynamic Effects of MEDI0382 in Obese Subjects With Non-Alcoholic Fatty Liver Disease (NAFLD)/ Non-Alcoholic Steatohepatitis (NASH)

MedImmune LLC1 site in 1 country74 target enrollmentSeptember 23, 2019

ConditionsNon-alcoholic Fatty Liver Disease (NAFLD)Non-alcoholic Steatohepatitis (NASH)

InterventionsMEDI0382 high dose Placebo for MEDI0382 high dose MEDI0382 low dose Placebo for MEDI0382 low dose

DrugsMEDI0382 high dose Placebo for MEDI0382 high dose MEDI0382 low dose Placebo for MEDI0382 low dose

Overview

Phase: Phase 2
Intervention: MEDI0382 high dose
Conditions: Non-alcoholic Fatty Liver Disease (NAFLD)
Sponsor: MedImmune LLC
Enrollment: 74
Locations: 1
Primary Endpoint: Safety (Including Hepatic Safety) and Tolerability of MEDI0382 Compared With Placebo: Number of Participants With TEAE and SAE
Status: Completed
Last Updated: 3 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

A Phase 2 study with 4 treatment groups of two differing doses and matched placebos designed to evaluate the safety (including hepatic safety), tolerability and pharmacodynamic effects of two dose levels of MEDI0382 in obese subjects with non-alcoholic fatty liver disease (NAFLD)/non-alcoholic steatohepatitis (NASH). The subjects will have biopsy-confirmed NAFLD/NASH with liver fibrosis stage F1, F2 or F3. Approximately 72 subjects will be randomized

Detailed Description

This is a randomized, double-blind, placebo-controlled, study to evaluate the safety (including hepatic safety), tolerability and pharmacodynamic effects of two dose levels of MEDI0382 in obese subjects with non-alcoholic fatty liver disease (NAFLD)/non-alcoholic steatohepatitis (NASH). The subjects will have biopsy-confirmed NAFLD/NASH with liver fibrosis stage F1, F2 or F3. Approximately 72 subjects will be randomized across multiple study sites.

Registry

clinicaltrials.gov

Start Date

September 23, 2019

End Date

May 6, 2021

Last Updated

3 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

MedImmune LLC

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Provision of informed consent (with the exception of consent for future genetic and non genetic research) prior to performing any study-specific procedures, including screening evaluations.
•Subjects aged ≥ 18 years at the time of consent.
•Body mass index ≥ 30 kg/m2 at screening.
•HbA1c ≤ 9.5% (inclusive) at screening if T2DM present, managed by either diet and/or a stable dose of metformin, sodium-glucose co-transporter 2 (SGLT-2) inhibitors, sulphonylureas or acarbose (ie, no major dose adjustments in prior 3 months to screening).
•Definitive NAFLD / NASH with NASH activity score (NAS) ≥ 4 with ≥ 1 in each component (i.e. steatosis, lobular inflammation and ballooning), as diagnosed by liver biopsy within 6 months of screening with liver fibrosis stage F1, F2 or F
•The number of subjects with F1 will be capped at 25% in the study.
•Evidence of hepatic steatosis or liver fat (≥ 10%) by MRI.
•Women of childbearing potential:
•Who are sexually active with a non-sterilized male partner must have used at least one highly effective method of contraception from screening, and must agree to continue using such precautions through to the end of the study. It is strongly recommended for the male partner of a female subject to also use male condom plus spermicide throughout this period. Cessation of contraception after this point should be discussed with a responsible physician. Periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of contraception.
•Must have a negative urine pregnancy test within 72 hours prior to the first dose of investigational product; and not be breastfeeding.

Exclusion Criteria

•History of, or any existing condition that, in the opinion of the investigator, would interfere with evaluation of the investigational product, put the subject at risk, influence the subject's ability to participate or affect the interpretation of the results of the study.
•Liver disease of other etiologies (eg, alcoholic steatohepatitis; drug-induced, viral, or autoimmune hepatitis; primary biliary cirrhosis; primary sclerosing cholangitis; hemochromatosis; alpha 1 antitrypsin deficiency; Wilson's disease) including positive results for hepatitis B surface antigen (HBsAg) or hepatitis C antibody tests (anti-HCV).
•History of cirrhosis and/or hepatic decompensation, including ascites, hepatic encephalopathy or variceal bleeding.
•Prior or planned liver transplantation.
•Alcohol consumption \> 21 units of alcohol per week for men and \> 14 units per week for women on average over a two-year time frame prior to baseline biopsy.
•Evidence of alcohol dependence as assessed by the Alcohol Use Disorder Identification Test (AUDIT) questionnaire at screening
•A history of type 1 diabetes mellitus (T1DM), a history of diabetic ketoacidosis or current use of insulin-based therapies.
•Clinically significant inflammatory bowel disease or other severe disease or surgery affecting the upper GI tract (including bariatric surgery) which may affect gastric emptying or could affect the interpretation of safety and tolerability data
•Physician-diagnosed diabetic subjects with clinically significant gastroparesis (as judged by the investigator) or those treated for gastroparesis within 6 months prior to screening
•History of \> 5 kg weight loss in the last 6 months prior to screening or recent (within 3 months of screening) use of drugs approved for weight loss (eg, orlistat, bupropion / naltrexone, phentermine-topiramate, phentermine, lorcaserin), as well as those drugs used off-label.

Arms & Interventions

MEDI0382 high dose

MEDI0382 high dose administered subcutaneously

Intervention: MEDI0382 high dose

Placebo for MEDI0382 high dose

Placebo for MEDI0382 high dose administered subcutaneously

Intervention: Placebo for MEDI0382 high dose

MEDI0382 low dose

MEDI0382 low dose administered subcutaneoously

Intervention: MEDI0382 low dose

Placebo for MEDI0382 low dose

Placebo for MEDI0382 low dose administered subcutaneously

Intervention: Placebo for MEDI0382 low dose

Outcomes

Primary Outcomes

Safety (Including Hepatic Safety) and Tolerability of MEDI0382 Compared With Placebo: Number of Participants With TEAE and SAE

Time Frame: Day 1 - Day 161

The number and percentage of treatment emergent adverse events (TEAE) and serious adverse events (SAE) through the end of the follow-up period

Secondary Outcomes

Immunogenicity Profile Defined by Presence of Anti-drug Antibodies (ADA): ADA Titer (if Confirmed Positive)(Day 1 - Day 161 (Baseline, Week 6, Week 12, Week 16, Week 19 and Week 23))
Percent Change From Baseline to Week 19 in Visceral Adipose Tissue(Baseline to week 19)
Percent Change From Baseline to Week 19 in Body Weight(Baseline to week 19)
Immunogenicity Profile Defined by Presence of Anti-drug Antibodies (ADA): Number of Participants With Development of ADA(Day 1 - Day 161)
Percent Change From Baseline to Week 19 in Subcutaneous Adipose Tissue(Baseline to week 19)
Percent Change From Baseline to Week 19 in Liver Diffusion(Baseline to week 19)
Percent Change From Baseline to Week 19 in Alanine Aminotransferase (ALT)(Baseline to week 19)
Percent Change From Baseline to Week 19 in Gamma Glutamyl Transferase (GGT)(Baseline to week 19)
Change From Baseline to Week 19 in Hepatic Fat Fraction (HFF)(Baseline to week 19)
Percent Change From Baseline to Week 19 in Liver Volume(Baseline to week 19)
Percent Change From Baseline to Week 19 in Liver Fat Volume(Baseline to week 19)
Percent Change From Baseline to Week 19 in Aspartate Aminotransferase (AST)(Baseline to week 19)
Percent Change From Baseline to Week 19 in Abdominal Sagittal Diameter(Baseline to week 19)
Percent Change From Baseline to Week 19 in Abdominal Transversal Diameter(Baseline to week 19)
Change From Baseline to Week 19 in Body Mass Index (BMI)(Baseline to week 19)